Diet is presumed to play a major role in prostate cancer - a leading cancer among American men. Yet, to date there are no dietary interventions with proven efficacy for either prevention or complementary care. The proposed study will focus on flaxseed supplementation (FS) and a low fat diet (LF), since our pilot studies and the research of others suggest that these factors significantly alter prostate cancer progression. Our multidisciplinary team of nutritionists, urologists, pathologists and biostatistians propose a controlled clinical trial to test the effects of FS and LF on prostatic neoplasia and also explore potential hormonal mechanisms. Newly diagnosed, prostate cancer cases (N=160) who have greater than 3-week lag- time prior to prostatectomy will be block randomized into one of the following groups: 1) control; 2) FS (30 g/day); LF (less than or equal to 20 percent total energy); or 4) FS+LF. All subjects will be monitored and receive dietary instruction and supplies. Proliferation rate (MIB-1) will serve as the primary endpoint to determine diet efficacy. Other endpoints include: apoptotic index (TUNEL), extent of high grade prostatic intraepithelial neoplasia and total serum prostate specific antigen. Given our pilot data which suggest that FS and LF diets may operate via a hormonal mechanism, potential hormonal mediators also will be assessed [i.e., total serum testosterone, free androgen index, insulin-like growth factor-1 (IGF-1) and IGF binding protein-3]. Nutritional biomarkers (i.e., lignan levels in prostatic fluid and urine, and erythrocyte and prostate fatty acid profiles) also will be measured. Associations between nutritional biomarkers, hormonal mediators and study endpoints will be determined. The proposed study is structured to make an important contribution to what is known about diet and prostatic neoplasia. This research has the potential to expand the scope of complementary treatment offered for prostate cancer, and may provide a solid foundation for efforts aimed at prevention.